GW-7845
2(S)-[2-(甲氧基羰基)苯胺基]-3-[4-[2-(5-甲基-2-苯氯佐尔-4-基)乙氧基]苯基]丙酸Chemical Name: 2(S)-[2-(Methoxycarbonyl)phenylamino]-3-[4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl]propionic acid
CAS No. 196809-22-0
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Oxazolylethanol (I) was coupled to N-Boc-L-tyrosine methyl ester (II) using Mitsunobu conditions in the presence of PPh3 and DEAD to give ether (III).Subsequent deprotection of the Boc group of (III) with trifluoroacetic acid afforded amine (IV),which was then condensed with methyl cyclohexanone-2-carboxylate (V) in boiling toluene to yield enamine (VI).Further heating of (VI) at 190 C in anisole in the presence of Pd/C resulted in aromatization of the cyclohexene ring to produce the anthranilate derivative (VII).Finally,selective hydrolysis of the aliphatic ester with LiOH under careful conditions provided the target monoester.
📌 参考资料/链接：
参考文献标题:N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists.3.Structure-activity relationship and optimization of the N-aryl substituent
文献作者:Cobb,J.E.; Blanchard,S.G.; Boswell,E.G.; Brown,K.K.; Charifson,P.S.; Cooper,J.P.; Collins,J.L.; Dezube,M.; Henke,B.R.; Hull-Ryde,E.A.; Lake,D.H.; Lenhard,J.M.; Oliver,W.Jr.; Oplinger,J.; Pentti,M.; Parks,D.J.; Plunket,K.D.; Tong,W.Q.
参考来源:J Med Chem 1998,41(25),5055